U.S. patent application number 12/021647 was filed with the patent office on 2009-07-30 for pain relief lollipop compositions and methods.
This patent application is currently assigned to Innovative Pharmaceuticals, LLC. Invention is credited to David J. Smith.
Application Number | 20090191257 12/021647 |
Document ID | / |
Family ID | 40899481 |
Filed Date | 2009-07-30 |
United States Patent
Application |
20090191257 |
Kind Code |
A1 |
Smith; David J. |
July 30, 2009 |
PAIN RELIEF LOLLIPOP COMPOSITIONS AND METHODS
Abstract
A pain relief lollipop comprises a candy matrix comprising (a)
an opioid agonist, (b) an N-methyl-D-aspartate receptor antagonist
different from the opioid agonist, (c) gabapentin, or a
pharmaceutically acceptable salt thereof, and, optionally, a muscle
relaxant, sedative, anxiolytic, and/or antidepressant. A patient
can self-administer small amounts of the pain relief drug as needed
by simply licking or sucking on the lollipop in response to his
subjective experience of pain.
Inventors: |
Smith; David J.; (San Diego,
CA) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET, FOURTEENTH FLOOR
IRVINE
CA
92614
US
|
Assignee: |
Innovative Pharmaceuticals,
LLC
San Diego
CA
|
Family ID: |
40899481 |
Appl. No.: |
12/021647 |
Filed: |
January 29, 2008 |
Current U.S.
Class: |
424/440 |
Current CPC
Class: |
A61K 45/06 20130101;
A61K 9/0056 20130101; A61P 25/04 20180101; A61K 31/195 20130101;
A61K 31/195 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/440 |
International
Class: |
A61K 9/00 20060101
A61K009/00; A61P 25/04 20060101 A61P025/04 |
Claims
1. A pain relief lollipop, comprising: a candy matrix comprising
(a) an opioid agonist, (b) an N-methyl-D-aspartate receptor
antagonist different from the opioid agonist, and (c) gabapentin or
a pharmaceutically acceptable salt thereof; and a holder in contact
with the candy matrix.
2. The pain relief lollipop of claim 1 in which the opioid agonist
is selected from the group consisting of fentanyl, hydromorphone,
hydrocodone, ketamine, methadone, oxycodone, oxymorphone,
propoxyphene, sulfentanil, and pharmaceutically acceptable salts
thereof.
3. The pain relief lollipop of claim 1 in which the
N-methyl-D-aspartate receptor antagonist is selected from the group
consisting of amantadine, D,L-2-amino-5-phosphono-valeric acid,
dextromethorphan, ketamine, methadone, and pharmaceutically
acceptable salts thereof.
4. The pain relief lollipop of claim 1, wherein: the opioid agonist
is selected from the group consisting of fentanyl, hydromorphone,
hydrocodone, oxycodone, oxymorphone, propoxyphene, sulfentanil, and
pharmaceutically acceptable salts thereof; and the
N-methyl-D-aspartate receptor antagonist is selected from the group
consisting of amantadine, dextromethorphan, and pharmaceutically
acceptable salts thereof.
5. The pain relief lollipop of claim 4 in which the candy matrix
further comprises a muscle relaxant.
6. The pain relief lollipop of claim 5 in which the muscle relaxant
is selected from the group consisting of alprazolam, butalbital,
clonazepam, carisoprodol, diazepam, flexeril, lorazepam,
methocarbamol, and pharmaceutically acceptable salts thereof.
7. The pain relief lollipop of claim 4 in which the candy matrix
further comprises a sedative.
8. The pain relief lollipop of claim 7 in which the sedative is
selected from the group consisting of clonazepam, butalbital,
diazepam, phenobarbital, and pharmaceutically acceptable salts
thereof.
9. The pain relief lollipop of claim 4 in which the candy matrix
further comprises an anxiolytic.
10. The pain relief lollipop of claim 9 in which the anxiolytic is
selected from the group consisting of alprazolam, clonazepam,
diazepam, lorazepam, and pharmaceutically acceptable salts
thereof.
11. The pain relief lollipop of claim 4 in which the candy matrix
further comprises an antidepressant.
12. The pain relief lollipop of claim 11 in which the
antidepressant is a tricyclic antidepressant selected from the
group consisting of amitriptyline, amoxapine, desipramine, doxepin,
imipramine, maprotiline, nortriptyline, protriptyline,
trimipramine, and pharmaceutically acceptable salts thereof.
13. The pain relief lollipop of claim 4 in which the candy matrix
further comprises at least two different medicaments selected from
the group consisting of a muscle relaxant, a sedative, an
anxiolytic and a tricyclic antidepressant.
14. The pain relief lollipop of claim 13 in which the muscle
relaxant is selected from the group consisting of alprazolam,
butalbital, clonazepam, diazepam, flexeril, lorazepam,
methocarbamol, and pharmaceutically acceptable salts thereof; in
which the sedative is selected from the group consisting of
clonazepam, butalbital, diazepam, phenobarbital, and
pharmaceutically acceptable salts thereof; in which the anxiolytic
is selected from the group consisting of alprazolam, clonazepam,
diazepam, lorazepam, and pharmaceutically acceptable salts thereof;
and in which the tricyclic antidepressant is selected from the
group consisting of amitriptyline, amoxapine, desipramine, doxepin,
imipramine, maprotiline, nortriptyline, protriptyline,
trimipramine, and pharmaceutically acceptable salts thereof.
15. A method for treating pain, comprising identifying a human
suffering from pain and administering the pain relief lollipop of
claim 1 to the human.
16. The method of claim 15, wherein the pain is chronic pain.
17. A method for making the pain relief lollipop of claim 1,
comprising intermixing the opioid agonist, N-methyl-D-aspartate
receptor antagonist, gabapentin or a pharmaceutically acceptable
salt thereof and candy matrix at a temperature effective to at
least partially melt the candy matrix to form an at least partially
molten lollipop mixture, molding the at least partially molten
lollipop mixture to form a molded lollipop mixture, contacting the
molded lollipop mixture with a holder, and cooling the molded
lollipop mixture to form a pain relief lollipop.
18. A method for making the pain relief lollipop of claim 1,
comprising intermixing the opioid agonist, N-methyl-D-aspartate
receptor antagonist, gabapentin or a pharmaceutically acceptable
salt thereof and candy matrix at a temperature effective to at
least partially melt the candy matrix to form an at least partially
molten lollipop mixture, molding the at least partially molten
lollipop mixture to form a molded lollipop mixture, cooling the
molded lollipop mixture to form an at least partially hardened
candy, and contacting the at least partially hardened candy with a
holder to form a pain relief lollipop.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] Embodiments of this invention relate to compositions useful
for alleviating pain and systems for their delivery to humans.
Preferred embodiments relate to pain relief lollipops that may be
used to provide oral transmucosal delivery of opioid agonists, NMDA
receptor antagonists, and gabapentin, or a pharmaceutically
acceptable salt thereof.
[0003] 2. Description of the Related Art
[0004] The treatment of physical pain concerns health care
professionals throughout the world. The treatment of chronic pain
is particularly challenging because of the frequent need for
repeated administration of pain relief medication. Chronic pain is
generally considered to be pain that continues a month or more
beyond the usual recovery period for an illness or injury or pain
that goes on over months or years as a result of a chronic
condition. It may be continuous or come and go. It is estimated
that chronic pain disables, to some degree, about 86 million
Americans. It is regarded as a source of frustration for the health
care professionals who care for the patient, and affects the
quality of life and economic security not only of the person with
pain, but also his or her family. It is estimated that United
States business and industry loses about $90 billion annually to
sick time, reduced productivity, and direct medical and other
benefit costs due to chronic pain among employees. In some cases,
repeated administration of the pain relief medication causes
sufferers of chronic pain to develop an undesirable tolerance or
addiction, creating further health issues for the patient and
additional challenges for the health care professional.
[0005] There are a number of methods for administering pain relief
medications, including oral and parenteral (administered in a
manner other than through the digestive tract). Oral administration
is most frequently accomplished by formulating the pain relief
medication into tablet or syrup and allowing the patient to swallow
it. This method is simple, well accepted and relatively painless,
but may be problematic for uncooperative patients. Also, there is
often a considerable lapse of time between administration of the
pain relief medication and its therapeutic effect because of the
time needed for gastrointestinal absorption. This time lag is of
particular concern when a patient is suffering from severe or
chronic pain. Faster administration may be accomplished by direct
injection of the pain relief medication, but most people consider
the injection itself to be painful and thus undesirable. What is
needed is a method for administering a variety of pain relief
formulations that is fast, well tolerated and relatively
painless.
SUMMARY OF THE INVENTION
[0006] Preferred embodiments are directed towards pain relief
delivery systems and methods and, in particular, lollipops and
methods of using them for the relief of pain. Preferred lollipops
are capable of introducing a pain relief drug into a patient's
system faster than a pain relief drug taken orally and without the
pain and invasiveness of an injection. Unlike the ordinary oral
ingestion of pain medication or injections where a relatively large
dose is given intermittently, use of a pain relief lollipop may
permit the patient to take relatively small doses of pain relief
medication on an almost continuous basis. A patient may
self-administer small amounts of the pain relief drug as needed by
simply licking or sucking on the lollipop in response to his or her
subjective experience of pain. These significant advantages can be
achieved by incorporating pain relief drugs into a candy mixture
capable of being absorbed by the patient through the mucosal tissue
of the mouth, pharynx and esophagus. The candy and pain relief drug
is molded into a lollipop form, which, as discussed more
specifically hereinafter, may be administered by the patient as
needed for pain relief.
[0007] Preferred pain relief drugs are opioid agonists. To inhibit
the development of tolerance and/or addiction to the opioid
agonists by the patient, preferred lollipops further comprise a
substance that blocks the N-methyl-D-aspartate receptor, herein
referred to as an "NMDA receptor antagonist." Preferred lollipops
further comprise gabapentin, or a pharmaceutically acceptable salt
thereof. In some embodiments, lollipops also contain a muscle
relaxant, a sedative, an anxiolytic, and/or tricyclic
antidepressant, to provide further comfort and relief for the
patient.
[0008] Some embodiments are directed to a pain relief lollipop,
comprising a candy matrix comprising (a) an opioid agonist, (b) an
N-methyl-D-aspartate receptor antagonist different from the opioid
agonist, and (c) gabapentin or a pharmaceutically acceptable salt
thereof; and a holder in contact with the candy matrix. In some
aspects, the opioid agonist is selected from the group consisting
of fentanyl, hydromorphone, hydrocodone, ketamine, methadone,
oxycodone, oxymorphone, propoxyphene, sulfentanil, and
pharmaceutically acceptable salts thereof. In some aspects, the
N-methyl-D-aspartate receptor antagonist is selected from the group
consisting of amantadine, D,L-2-amino-5-phosphono valeric acid,
dextromethorphan, ketamine, methadone, and pharmaceutically
acceptable salts thereof.
[0009] Other embodiments are directed to a method for treating
pain, comprising identifying a human suffering from pain and
administering a pain relief lollipop described in the various
embodiments herein. Some aspects of the embodiment are directed
towards the treatment of chronic pain.
[0010] Still other embodiments are directed to a method for making
a pain relief lollipop described in the various embodiments herein,
comprising intermixing the opioid agonist, N-methyl-D-aspartate
receptor antagonist, gabapentin or a pharmaceutically acceptable
salt thereof, and candy matrix at a temperature effective to at
least partially melt the candy matrix to form an at least partially
molten lollipop mixture, molding the at least partially molten
lollipop mixture to form a molded lollipop mixture, contacting the
molded lollipop mixture with a holder, and cooling the molded
lollipop mixture to form a pain relief lollipop.
[0011] Other embodiments are directed to a method for making a pain
relief lollipop described in the various embodiments herein,
comprising intermixing the opioid agonist, N-methyl-D-aspartate
receptor antagonist, gabapentin or a pharmaceutically acceptable
salt thereof and candy matrix at a temperature effective to at
least partially melt the candy matrix to form an at least partially
molten lollipop mixture, molding the at least partially molten
lollipop mixture to form a molded lollipop mixture, cooling the
molded lollipop mixture to form an at least partially hardened
candy, and contacting the at least partially hardened candy with a
holder to form a pain relief lollipop.
[0012] Still other embodiments are directed to a pain relief
lollipop, comprising a candy matrix comprising (a) an opioid
agonist, (b) an N-methyl-D-aspartate receptor antagonist different
from the opioid agonist, and (c) gabapentin or a pharmaceutically
acceptable salt thereof; and a means for holding the candy
matrix.
[0013] Other embodiments are directed to a pain relief lollipop,
comprising a candy matrix comprising (a) an opioid agonist selected
from the group consisting of fentanyl, hydromorphone, hydrocodone,
oxycodone, oxymorphone, propoxyphene, sulfentanil, and
pharmaceutically acceptable salts thereof, (b) an
N-methyl-D-aspartate receptor antagonist selected from the group
consisting of amantadine, dextromethorphan, and pharmaceutically
acceptable salts thereof, and (c) gabapentin or a pharmaceutically
acceptable salt thereof; and a holder in contact with the candy
matrix. In some aspects, the candy matrix further comprises a
muscle relaxant, wherein the muscle relaxant can be selected from
the group consisting of alprazolam, butalbital, clonazepam,
carisoprodol, diazepam, flexeril, lorazepam, methocarbamol, and
pharmaceutically acceptable salts thereof. In some aspects, the
candy matrix further comprises a sedative, wherein the sedative can
be selected from the group consisting of clonazepam, butalbital,
diazepam, phenobarbital, and pharmaceutically acceptable salts
thereof. In other aspects, the candy matrix further comprises an
anxiolytic, wherein the anxiolytic can be selected from the group
consisting of alprazolam, clonazepam, diazepam, lorazepam, and
pharmaceutically acceptable salts thereof. In still other aspects,
the candy matrix further comprises an antidepressant, wherein the
antidepressant can be a tricyclic antidepressant selected from the
group consisting of amitriptyline, amoxapine, desipramine, doxepin,
imipramine, maprotiline, nortriptyline, protriptyline,
trimipramine, and pharmaceutically acceptable salts thereof. In yet
other aspects, the candy matrix further comprises at least two
different medicaments selected from the group consisting of a
muscle relaxant, a sedative, an anxiolytic and a tricyclic
antidepressant, wherein the muscle relaxant can be selected from
the group consisting of alprazolam, butalbital, clonazepam,
diazepam, flexeril, lorazepam, methocarbamol, and pharmaceutically
acceptable salts thereof; in which the sedative can be selected
from the group consisting of clonazepam, butalbital, diazepam,
phenobarbital, and pharmaceutically acceptable salts thereof; in
which the anxiolytic can be selected from the group consisting of
alprazolam, clonazepam, diazepam, lorazepam, and pharmaceutically
acceptable salts thereof; and in which the tricyclic antidepressant
can be selected from the group consisting of amitriptyline,
amoxapine, desipramine, doxepin, imipramine, maprotiline,
nortriptyline, protriptyline, trimipramine, and pharmaceutically
acceptable salts thereof.
[0014] These and other embodiments are described in greater detail
below.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] Preferred compositions provide lollipop compositions and
methods for using them to treat pain. In this context, "lollipop"
is used in its ordinary sense to refer to a piece of candy in
operable contact with a holder. Preferably, the candy is supported
by, held by, or attached to the holder to provide operable contact.
Non-limiting examples of holders include a stick or string
partially embedded in or attached to the candy, and a platform such
as a cone that supports the candy.
[0016] To provide pain relief to the consumer of the lollipop, the
candy preferably comprises an opioid agonist. In this context,
"opioid agonist" is used in the ordinary sense to refer to opiates,
opiate derivatives, opioids, and other substances whose effects are
mediated by the same receptor, and includes mixtures thereof.
Non-limiting examples of preferred opioid agonists include
fentanyl, hydromorphone, hydrocodone, ketamine, methadone,
oxycodone, oxymorphone, propoxyphene, sulfentanil, and
pharmaceutically acceptable salts thereof.
[0017] The amount of opioid agonist in the lollipop is an amount
that is effective to reduce the patient's pain, and will generally
vary depending on the type and amount of pain experienced by the
patient, the characteristics of the patient, and the efficacy of
the particular opioid agonist. Dosages of particular opioid
agonists useful for treating pain are known to those skilled in the
art, see, e.g., Physician's Desk Reference 2003, which is hereby
incorporated by reference in its entirety and particularly for the
purpose of describing typical dosages of opioid agonists, NMDA
receptor antagonists, muscle relaxants, sedatives, anxiolytics and
antidepressants. Dosages may also be determined by routine
experimentation. Such known or determined dosages of opioid agonist
may be used as a guideline for determining the amount of opioid
agonist to include in the lollipop, typically taking into account
various patient characteristics (e.g., level of pain, age, weight,
and overall health) in a manner known to those skilled in the
medical arts, as well as the characteristics of the lollipop (e.g.,
rate of dissolution) and the transmucosal delivery characteristics
of the particular opioid agonist.
[0018] To avoid or reduce the development of tolerance and/or
dependence by the patient on the opioid agonist, the lollipop candy
preferably comprises an NMDA receptor antagonist different from the
opioid agonist. NMDA receptor antagonists are substances known to
those skilled in the art that block the N-methyl-D-aspartate
receptor or that block a major intracellular consequence of NMDA
receptor activation, see U.S. Pat. Nos. 5,321,012; 5,654,281 and
5,869,498, all of which are hereby incorporated by reference in
their entireties, and particularly for the purpose of describing
NMDA receptor antagonists and their uses. The NMDA receptor
antagonist may be a mixture. Non-limiting examples of preferred
NMDA receptor antagonists for inclusion in the lollipop include
amantadine, D,L-2-amino-5-phosphono valeric acid, dextromethorphan,
ketamine, methadone, and pharmaceutically acceptable salts thereof.
Since some substances, e.g., ketamine and methadone, may be
classified as both opioid agonists and NMDA receptor antagonists,
it is understood that the opioid agonist in any particular lollipop
is different from the NMDA receptor antagonist.
[0019] The amount of NMDA receptor antagonist in the lollipop is an
amount that is effective to avoid or reduce the development of
tolerance and/or dependence by the patient on the opioid agonist,
and will generally vary depending on the type and amount of the
particular opioid agonist present in the lollipop and on the
effectiveness of the particular NMDA receptor antagonist. Dosages
of particular NMDA receptor antagonists useful for avoiding or
reducing the development of tolerance and/or dependence to a
particular opioid agonist are known to those skilled in the art,
see, e.g., Physician's Desk Reference 2003, or may be determined by
routine experimentation. Such known or determined dosages of NMDA
receptor antagonist may be used as a guideline for determining the
amount of the NMDA receptor antagonist to include in the lollipop,
typically taking into account various patient characteristics
(e.g., level of pain, age, weight, and overall health) in a manner
known to those skilled in the medical arts, as well as the
characteristics of the lollipop (e.g., rate of dissolution) and the
transmucosal delivery characteristics of the particular NMDA
receptor antagonist.
[0020] To provide further relief from pain, especially chronic
pain, to the consumer of the lollipop, the candy preferably
comprises gabapentin, or a pharmaceutically acceptable salt
thereof. Gabapentin is an anti-convulsant originally developed for
the treatment of epilepsy. The use of gabapentin in the lollipop
compositions described herein can complement the use of opioid
analgesics to provide more complete relief from neuropathic
pain.
[0021] The amount of gabapentin, or a pharmaceutically acceptable
salt thereof, in the lollipop is an amount that is effective to
reduce the patient's pain, and will generally vary depending on the
type and amount of pain experienced by the patient, and the
characteristics of the patient. Dosages of gabapentin useful for
treating pain are known to those skilled in the art, see, e.g.,
Physician's Desk Reference 2003, which is hereby incorporated by
reference in its entirety and particularly for the purpose of
describing typical dosages of gabapentin, opioid agonists, NMDA
receptor antagonists, muscle relaxants, sedatives, anxiolytics and
antidepressants. Dosages may also be determined by routine
experimentation. Such known or determined dosages of gabapentin may
be used as a guideline for determining the amount of gabapentin, or
a pharmaceutically acceptable salt thereof, to include in the
lollipop, typically taking into account various patient
characteristics (e.g., level of pain, age, weight, and overall
health) in a manner known to those skilled in the medical arts, as
well as the characteristics of the lollipop (e.g., rate of
dissolution) and the transmucosal delivery characteristics of the
gabapentin, or a pharmaceutically acceptable salt thereof.
[0022] For example, a preferred pain relief lollipop comprises a
candy matrix comprising (a) an opioid agonist selected from the
group consisting of fentanyl, hydromorphone, hydrocodone,
oxycodone, oxymorphone, propoxyphene, sulfentanil, and
pharmaceutically acceptable salts thereof, (b) an
N-methyl-D-aspartate receptor antagonist selected from the group
consisting of amantadine, dextromethorphan, and pharmaceutically
acceptable salts thereof; (c) gabapentin, or a pharmaceutically
acceptable salt thereof, and a holder in contact with the candy
matrix.
[0023] Pain relief lollipops may optionally contain additional
medicaments to provide further comfort and/or relief to the
patient, and/or to treat specific conditions such a muscle tension,
overexcitement, anxiety and/or depression. Preferably, the lollipop
candy further comprises a medicament selected from the group
consisting of a muscle relaxant, a sedative, an anxiolytic and an
antidepressant, the medicament being different from the opioid
agonist and different from the N-methyl-D-aspartate receptor
antagonist. The terms "muscle relaxant," "sedative," "anxiolytic"
and "antidepressant" are known to those skilled in the art, see,
e.g., Physician's Desk Reference 2003 and Dorland's Illustrated
Medical Dictionary, W.B. Saunders Co., 2000, and include mixtures
thereof. Non-limiting examples of preferred muscle relaxants
include alprazolam, butalbital, clonazepam, carisoprodol, diazepam,
flexeril, lorazepam, methocarbamol, and pharmaceutically acceptable
salts thereof. Non-limiting examples of sedatives include
clonazepam, butalbital, diazepam, phenobarbital, and
pharmaceutically acceptable salts thereof. Non-limiting examples of
anxiolytics include alprazolam, clonazepam, diazepam, lorazepam,
and pharmaceutically acceptable salts thereof. Non-limiting
examples of antidepressants include tricyclic antidepressants and
monamine oxidase inhibitors. Non-limiting examples of preferred
tricyclic antidepressants include amitriptyline, amoxapine,
desipramine, doxepin, imipramine, maprotiline, nortriptyline,
protriptyline, trimipramine, and pharmaceutically acceptable salts
thereof. Those skilled in the art recognize that some substances
may have multiple classifications (e.g., alprazolam as both a
muscle relaxant and an anxiolytic). It is therefore understood that
reference herein to a lollipop that contains three or more
medicaments selected from the group consisting of opioid agonist,
NMDA receptor antagonist, muscle relaxant, sedative, anxiolytic and
antidepressant, means that each of the three or more medicaments
are different from one another.
[0024] The amount and type of additional medicament (e.g., muscle
relaxant, sedative, anxiolytic and/or antidepressant) in the
lollipop, if any, is an amount that is effective to provide
additional comfort and/or relief to the patient from various
conditions, and will generally vary depending on the type and
amount of the particular additional medicament present in the
lollipop. Dosages of particular additional medicaments useful for
treating various conditions are known to those skilled in the art,
see, e.g., Physician's Desk Reference 2003, or may be determined by
routine experimentation. Such known or determined dosages of
additional medicaments may be used as a guideline for determining
the amount of the additional medicament(s) to include in the
lollipop, typically taking into account various patient
characteristics (e.g., level of muscle tension, overexcitement,
anxiety and/or depression, age, weight, and overall health) in a
manner known to those skilled in the medical arts, as well as the
characteristics of the lollipop (e.g., rate of dissolution) and the
transmucosal delivery characteristics of the particular
medicament(s).
[0025] Pain relief lollipops are preferably made by intermixing the
medicaments (e.g., opioid agonist, NMDA receptor antagonist,
gabapentin, or a pharmaceutically acceptable salt thereof, and,
optionally, muscle relaxant, sedative, anxiolytic and/or
antidepressant) with the other non-medicinal lollipop ingredients
(e.g., candy, sorbitol, flavoring, coloring, etc.) during the
making of the lollipops. The non-medicinal lollipop ingredients are
preferably selected to slowly dissolve and/or melt in the patient's
mouth in a manner similar to that of a traditional lollipop, so as
to release the medicaments over the course of dissolution and/or
melting. The medicaments may be incorporated into the lollipop in
other ways, e.g. by coating onto the exterior of a lollipop, but
incorporation during manufacture is generally preferable so that
the medicaments are more uniformly dispersed throughout the
resulting candy matrix. Such relatively uniform dispersal has been
found to provide a corresponding uniform release and subsequent
transmucosal absorption of the medicaments during administration of
the lollipop to the patient.
[0026] Methods for making conventional lollipops are well known in
the art. A preferred embodiment of the invention provides a method
for making a pain relief lollipop, comprising intermixing the
various medicaments and non-medicinal ingredients in the molten or
partially molten state by heating the ingredients to a temperature
effective to melt or partially melt at least part of the
ingredients, preferably at a temperature in the range of about
35.degree. C. to about 95.degree. C., pouring the resulting molten
or partially molten lollipop mixture into a mold or molds, placing
a stick, string or other suitable object into the molded mixture so
that part protrudes to serve as a holder, and cooling the lollipop
mixture to form a hardened or semi-hardened candy attached to the
holder. In an alternative embodiment, the holder is placed in
contact with, e.g., attached to, the hardened or semi-hardened
candy after cooling. Various methods for making the lollipop may be
practiced according to the knowledge of those skilled in the art,
although extreme manufacturing conditions that significantly alter
the efficacy of the medicaments are to be avoided.
[0027] A preferred embodiment provides methods for treating pain,
comprising identifying a human suffering from pain and
administering a pain relief lollipop as described herein to the
human. Methods for identifying humans suffering from pain and
assessing the appropriate method of providing relief are known to
those skilled in the medical arts. Administration of the pain
relief lollipop is preferably by patient self-administration, e.g.,
by sucking or licking the lollipop, such that oral transmucosal
delivery of the various medicaments is facilitated. The pain relief
lollipop may be chewed and swallowed to provide gastrointestinal
delivery of the medicaments, but administration of the lollipop is
preferably conducted by advising the patient not to chew or swallow
pieces of the lollipop in order to provide preferred oral
transmucosal delivery. Other preferred embodiments comprise
identifying a patient suffering from pain as well as muscle
tension, overexcitement, anxiety and/or depression, and
administering a pain relief lollipop further comprising a muscle
relaxant, sedative, anxiolytic and/or antidepressant, to treat such
muscle tension, overexcitement, anxiety and/or depression,
respectively.
[0028] The pain relief lollipops described herein are particularly
useful for the treatment of patients suffering from chronic pain
because such treatment may involve multiple administrations over an
extended period of time. In such situations, the preferred pain
relief lollipops described herein may be used to provide numerous
benefits, including relief of the primary pain by the opioid
agonist and avoidance or reduction of the development of tolerance
and/or dependence by the patient to the opioid agonist, further
treatment of pain with gabapentin, or a pharmaceutically acceptable
salt thereof, as well as treatment of other conditions which may be
present such as muscle tension, overexcitement, anxiety and/or
depression, by the administration of additional medicaments such as
muscle relaxants, sedatives, anxiolytics and antidepressants,
respectively.
EXAMPLE 1
[0029] Eighteen suppository mold strips (each containing 12 molds)
in a metal-holding tray are set up on top of wax paper in a
vertical flow hood. The mold strips are sprayed with cooking oil
spray and a rubber spatula is used across the tops of the molds to
push oil inside. A spin bar is placed into a 500 milliliters (mL)
beaker and about 620 grams (g) of a commercially available sorbitol
lollipop base is added to the beaker. The contents are heated on a
hot plate at about 70.degree. C. with magnetic stirring to melt the
lollipop base. About 1.1 g of hydromorphone is weighed in the
barrel of a 20 mL syringe. Water and red food coloring are drawn
into the syringe and the resulting mixture is shaken to provide a
hydromorphone solution. The hydromorphone solution is then injected
into the melted lollipop base over the course of several minutes
with stirring. A uniform red color indicates complete dispersion of
the ingredients. The temperature of the molten mixture is reduced
to about 50.degree. C. A mixture of 0.55 g dextromethorphan, 0.35 g
silica gel, and 1.3 g sodium saccharin are intermixed and added to
the mixture in the beaker with stirring. About 22.5 g of gabapentin
is weighed in the barrel of a 50 ml syringe. Water is drawn into
the syringe and the resulting mixture is shaken to provide a
gabapentin solution. The gabapentin solution is added to the
mixture in the beaker with stirring. About 6 mL raspberry flavor
and about 3.6 mL wild cherry oil are then added with stirring to
the mixture in the beaker to form a lollipop solution. The lollipop
solution is then drawn into a 60 mL syringe, which is then used to
fill each of the 216 suppository molds. One end of a 2-3 inch
plastic stick is then placed near the center of each lollipop to
form a handle. The lollipops in the mold are then refrigerated
overnight then removed from the molds. Each of the resulting
lollipops contains about 4 milligrams (mg) of hydromorphone, about
2 mg of dextromethorphan and about 100 mg of gabapentin.
EXAMPLE 2
[0030] Eighteen suppository mold strips (each containing 12 molds)
in a metal-holding tray are set up on top of wax paper in a
vertical flow hood. The mold strips are sprayed with cooking oil
spray and a rubber spatula was used across the tops of the molds to
push oil inside. A spin bar is placed into a 500 mL beaker and
about 620 g of a commercially available sorbitol lollipop base is
added to the beaker. The contents are heated on a hot plate at
about 90.degree. C. with magnetic stirring to melt the lollipop
base. About 0.50 g of fentanyl citrate is weighed in the barrel of
a 20 mL syringe. Water and red food coloring are drawn into the
syringe and the resulting mixture is shaken to provide a
hydromorphone solution. The hydromorphone solution is then injected
into the melted lollipop base over the course of several minutes
with stirring. A uniform red color indicates complete dispersion of
the ingredients. The temperature of the molten mixture is reduced
to about 50.degree. C. A mixture of 0.55 g dextromethorphan, 0.35 g
silica gel, and 1.3 g sodium saccharin are intermixed and added to
the mixture in the beaker with stirring. About 22.5 g of gabapentin
is weighed in the barrel of a 50 ml syringe. Water is drawn into
the syringe and the resulting mixture is shaken to provide a
gabapentin solution. The gabapentin solution is added to the
mixture in the beaker with stirring. About 6 mL raspberry flavor
and about 3.6 mL wild cherry oil is then added with stirring to the
mixture in the beaker to form a lollipop solution. The lollipop
solution is then drawn into a 60 mL syringe, which is then used to
fill each of the 216 suppository molds. One end of a 2-3 inch
plastic stick is then placed near the center of each lollipop to
form a handle. The lollipops in the mold are then refrigerated
overnight then removed from the molds. Each of the resulting
lollipops contains about 1.25 mg of fentanyl, about 2 mg of
dextromethorphan and about 100 mg of gabapentin.
EXAMPLE 3
[0031] The procedure described in Example 2 is repeated except that
a smaller amount (0.42 g) of fentanyl citrate is used. Each of the
resulting lollipops contains about one mg of fentanyl, about 2 mg
of dextromethorphan and about 100 mg of gabapentin.
EXAMPLE 4
[0032] The procedure described in Example 2 is repeated except that
a smaller amount (0.22 g) of fentanyl citrate is used. Each of the
resulting lollipops contains about 500 micrograms of fentanyl,
about 2 mg of dextromethorphan and about 100 mg of gabapentin.
EXAMPLE 5
[0033] The procedure described in Example 2 is repeated except that
2.16 g of methocarbamol is added to the mixture of 0.55 g
dextromethorphan, 0.35 g silica gel, and 1.3 g sodium saccharin.
Each of the resulting lollipops contains about 1.25 mg of fentanyl,
10 mg methocarbamol, about 2 mg of dextromethorphan, and about 100
mg of gabapentin.
[0034] Although the foregoing invention has been described in terms
of certain preferred embodiments, other embodiments will become
apparent to those of ordinary skill in the art in view of the
disclosure herein. Accordingly, the invention is not intended to be
limited by the recitation of preferred embodiments, but is intended
to be defined solely by reference to the appended claims.
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